Cytoplasmic cleavage of IMPA1 3' UTR is necessary for maintaining axon integrity.
Cytoplasmic cleavage of IMPA1 3' UTR is necessary for maintaining axon integrity.
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DOI：
10.1016/j.celrep.2021.108778
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发表时间：
2021-02-23
期刊：
影响因子：
8.8
通讯作者：
Riccio A
中科院分区：
文献类型：
--
作者：
Andreassi C;Luisier R;Crerar H;Darsinou M;Blokzijl-Franke S;Lenn T;Luscombe NM;Cuda G;Gaspari M;Saiardi A;Riccio A
信使RNA（mRNAs）的3′非翻译区（3′ UTR）是一种非编码序列，参与mRNA代谢的许多方面，包括细胞内定位和翻译。mRNA的不正确加工和传递导致严重的发育缺陷，并与许多神经系统疾病有关。在这里，我们使用深度测序表明，在交感神经元轴突中，许多转录本的3′ UTR经历切割，产生表达编码序列的亚型，具有短的3′ UTR和稳定的3′ UTR衍生片段，功能未知。由含有内切核酸酶argonaute 2（Ago2）的蛋白复合物介导的肌醇单磷酸酶1（IMPA 1）的长3′ UTR的切割产生维持交感神经元轴突完整性所必需的可翻译同种型。因此，我们的研究提供了一种mRNA代谢机制，该机制同时调节局部蛋白质合成并产生另一类3′ UTR衍生的RNA。交感神经元的轴突和细胞体表达不同的3′ UTR亚型轴突特异性短的3 ′ UTR亚型是由较长的3′ UTR的局部切割产生的。含有Ago2、Upf 1、HuD和Pabpc 4的蛋白复合物介导3′ UTR切割。显示3′ UTR在交感神经元的轴突和细胞体中的广泛差异使用。在轴突中，Impa1较长的3′ UTR的切割产生了较短的异构体，该异构体是稳定的、多腺苷酸化的，并且是维持轴突完整性所必需的。
The 3′ untranslated regions (3′ UTRs) of messenger RNAs (mRNAs) are non-coding sequences involved in many aspects of mRNA metabolism, including intracellular localization and translation. Incorrect processing and delivery of mRNA cause severe developmental defects and have been implicated in many neurological disorders. Here, we use deep sequencing to show that in sympathetic neuron axons, the 3′ UTRs of many transcripts undergo cleavage, generating isoforms that express the coding sequence with a short 3′ UTR and stable 3′ UTR-derived fragments of unknown function. Cleavage of the long 3′ UTR of Inositol Monophosphatase 1 (IMPA1) mediated by a protein complex containing the endonuclease argonaute 2 (Ago2) generates a translatable isoform that is necessary for maintaining the integrity of sympathetic neuron axons. Thus, our study provides a mechanism of mRNA metabolism that simultaneously regulates local protein synthesis and generates an additional class of 3′ UTR-derived RNAs. Axons and cell bodies of sympathetic neurons express distinct 3′ UTR isoforms Axon-specific short 3′ UTR isoforms are generated by local cleavage of longer 3′ UTRs A protein complex containing Ago2, Upf1, HuD, and Pabpc4 mediates the 3′ UTR cleavage Andreassi et al. show widespread differential usage of 3′ UTR in axons and cell bodies of sympathetic neurons. In axons, the cleavage of a longer 3′ UTR of Impa1 generates a shorter isoform that is stable, polyadenylated, and necessary for maintaining axon integrity.
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影响因子：
14.9
作者：
Baugh, L. R.;Hill, A. A.;Hunter, Craig P.
通讯作者：
Hunter, Craig P.
影响因子：
16.2
作者：
Flavell, Steven W.;Kim, Tae-Kyung;Gray, Jesse M.;Harmin, David A.;Hemberg, Martin;Hong, Elizabeth J.;Markenscoff-Papadimitriou, Eirene;Bear, Daniel M.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
14.9
作者：
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通讯作者：
Searle SM
影响因子：
3.7
作者：
Allen M;Bird C;Feng W;Liu G;Li W;Perrone-Bizzozero NI;Feng Y
通讯作者：
Feng Y
影响因子：
16.2
作者：
Crerar, Hamish;Scott-Solomon, Emily;Riccio, Antonella
通讯作者：
Riccio, Antonella